Medical Book

LANGUAGE
English Español 中文 Українська
Search

Showing results for: Array

    Medical Book

    LANG
    English Español 中文 Українська
    LDL-C
    Home > Parameters

    LDL-C

    LDL cholesterol: how LDL causes atherosclerosis, ESC/EAS targets by cardiovascular risk, Friedewald formula and treatment.

    LDL cholesterol (LDL-C) is the cholesterol carried in low-density lipoproteins. LDL particles deliver cholesterol to cells, but when there are too many of them, they penetrate the artery wall, are retained and oxidised there, and start the formation of atherosclerotic plaque. LDL-C is the main target of lipid-lowering treatment. Its target value is not a single "norm": the higher a person's cardiovascular risk, the lower the target.

    Lipid profileAtherosclerosisTreatment targets
    Low risk< 3.0 mmol/L (116 mg/dL)
    High risk< 1.8 mmol/L (70 mg/dL)
    Very high risk< 1.4 mmol/L (55 mg/dL)
    Suspect FH≥ 4.9 mmol/L (190 mg/dL)
    Lipoprotein classes from largest to smallest: chylomicrons, VLDL, IDL, LDL and HDL, with their size, main lipid cargo and role in atherosclerosis Blood lipoproteins (not to scale) Chylo-VLDLIDLLDLHDL 75–1200 nm30–80 nm25–35 nm18–25 nm5–12 nm dietary TGliver TGTG + cholesterolmostly cholesterolcholesterol, protein remnants atherogenicatherogenicatherogenicmain atherogenicreverse transport apoB-100 on VLDL, IDL, LDL apoA-I on HDL ← larger, lighter, more triglyceride smaller, denser, more protein →
    Figure 1. LDL is the main cholesterol-carrying atherogenic particle. Each LDL particle carries one apolipoprotein B molecule.

    How LDL causes atherosclerosis

    LDL particles smaller than about 70 nm cross the inner lining of arteries. Particles retained in the wall are modified (oxidised) and taken up by macrophages, which turn into lipid-laden "foam cells". This is the beginning of a fatty streak that, over decades, grows into a plaque. When a plaque ruptures, a clot forms on it, causing a heart attack or stroke. The effect is cumulative: the total damage depends on both the LDL level and how many years the arteries are exposed to it.

    Target values (2019 ESC/EAS)

    Bar chart of LDL cholesterol goals by cardiovascular risk: low risk below 3.0, moderate below 2.6, high below 1.8 and very high below 1.4 millimoles per litre LDL-C goal by cardiovascular risk category (mmol/L) Low riskModerate riskHigh riskVery high risk < 3.0 < 2.6 < 1.8 and ≥ 50 % reduction < 1.4 and ≥ 50 % reduction Recurrent events within 2 years despite maximal statin: goal < 1.0 mmol/L may be considered
    Figure 2. The lower the overall cardiovascular risk, the higher the acceptable LDL-C. Risk is estimated from age, sex, blood pressure, smoking, cholesterol, diabetes, kidney function and established disease.

    How LDL-C is measured

    Many laboratories calculate LDL-C with the Friedewald formula: LDL-C = TC − HDL-C − TG / 2.2 (mmol/L), or TG / 5 in mg/dL. The formula is unreliable when triglycerides exceed 4.5 mmol/L (400 mg/dL) or LDL is very low. In those cases a direct measurement, newer formulas (Martin–Hopkins, Sampson), non-HDL cholesterol or apolipoprotein B are preferred.

    Causes of high LDL-C

    • Diet high in saturated and trans fats, excess weight, inactivity
    • Familial hypercholesterolaemia: LDL-C ≥ 4.9 mmol/L in adults (≥ 4 mmol/L in children), early heart disease in the family, tendon xanthomas
    • Hypothyroidism, nephrotic syndrome, cholestasis, pregnancy, some medicines

    Lowering LDL-C

    Lifestyle changes typically lower LDL-C by 5–15 %. These include a Mediterranean-type diet, less saturated fat, more fibre, weight loss and exercise. Statins lower it by 30–50 % or more; ezetimibe and PCSK9-targeting drugs reduce it further. Each 1 mmol/L reduction lowers major cardiovascular events by about one fifth, with no lower threshold of benefit found so far.

    What to do

    Ask your doctor to estimate your overall cardiovascular risk and your personal LDL-C target. Do not stop lipid-lowering medicines on your own. LDL-C of 4.9 mmol/L or more requires assessment for familial hypercholesterolaemia and testing of relatives.

    References

    1. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111–188. doi:10.1093/eurheartj/ehz455
    2. Ference BA, Ginsberg HN, Graham I, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017;38(32):2459–2472. doi:10.1093/eurheartj/ehx144
    3. Cholesterol Treatment Trialists' (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670–1681. doi:10.1016/S0140-6736(10)61350-5
    4. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18(6):499–502. doi:10.1093/clinchem/18.6.499

    This article is for general information and does not replace a consultation with a doctor. Laboratory results must be interpreted by a physician together with symptoms and other tests.

    Published on 1 July 2019